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Molecular targets on mast cells and basophils for novel therapies

Harvima, Ikka T., Levi-Schaffer, Francesca, Draber, Petr, Polakovikova, Iva, Gibbs, Bernhard F., Blank, Ulirch, Nilsson, Gunnar, Maurer, Marcus (2014) Molecular targets on mast cells and basophils for novel therapies. Journal of Allergy and Clinical Immunology, 134 (3). pp. 530-544. ISSN 0091-6749. (doi:10.1016/j.jaci.2014.03.007) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1016/j.jaci.2014.03.007

Abstract

Mast cells and basophils (MCs/Bs) play a crucial role in type I allergy, as well as in innate and adaptive immune responses. These cells mediate their actions through soluble mediators, some of which are targeted therapeutically by, for example, H1- and H2-antihistamines or cysteinyl leukotriene receptor antagonists. Recently, considerable progress has been made in developing new drugs that target additional MC/B mediators or receptors, such as serine proteinases, histamine 4-receptor, 5-lipoxygenase-activating protein, 15-lipoxygenase-1, prostaglandin D2, and proinflammatory cytokines. Mediator production can be abrogated by the use of inhibitors directed against key intracellular enzymes, some of which have been used in clinical trials (eg, inhibitors of spleen tyrosine kinase, phosphatidylinositol 3-kinase, Bruton tyrosine kinase, and the protein tyrosine kinase KIT). Reduced MC/B function can also be achieved by enhancing Src homology 2 domain-containing inositol 5' phosphatase 1 activity or by blocking sphingosine-1-phosphate. Therapeutic interventions in mast cell-associated diseases potentially include drugs that either block ion channels and adhesion molecules or antagonize antiapoptotic effects on B-cell lymphoma 2 family members. MCs/Bs express high-affinity IgE receptors, and blocking their interactions with IgE has been a prime goal in antiallergic therapy. Surface-activating receptors, such as CD48 and thymic stromal lymphopoietin receptors, as well as inhibitory receptors, such as CD300a, Fc?RIIb, and endocannabinoid receptors, hold promising therapeutic possibilities based on preclinical studies. The inhibition of activating receptors might help prevent allergic reactions from developing, although most of the candidate drugs are not sufficiently cell specific. In this review recent advances in the development of novel therapeutics toward different molecules of MCs/Bs are presented.

Item Type: Article
DOI/Identification number: 10.1016/j.jaci.2014.03.007
Projects: [UNSPECIFIED] Mast cells and Basophils: targets for innovative therapies
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Bernhard F. Gibbs
Date Deposited: 02 Dec 2014 17:43 UTC
Last Modified: 29 May 2019 13:49 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45702 (The current URI for this page, for reference purposes)
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